Our laboratories are concerned with the chemistry and biology of extracellular matrix and with the synergies between matrix and hormones in regulating cellular physiology. For a number of years we have been developing the technologies necessary to study the roles of matrix and hormones in regulating gene expression in a differentiated mammalian epithelioid cell, the hepatocytes, and in their neoplastic counterparts, the hepatomas. These technologies permit us to culture normal hepatocytes or hepatomas so that they either grow at maximal rates and with lower levels of liver-specific functions or are maintained as non-growing cells with higher levels of liver-specific functions. The technologies include the use of serum-free, hormonally defined media and substrata of extracts containing extracellular matrix referred to as biomatrix. At present, we are chemically dissecting the biomatrix to ascertain which molecules are responsible for its biological activity and using the information to form substrata composed of defined and purified matrix components. The initial studies have utilized known matrix components alone and in various combinations. After optimization of these cultures with their components, we will turn to the biomatrix extracts as a source material for the purification of other matrix components with biological activity. The project involves the technologies of both biology and chemistry, so we have fused the expertise of Dr. L. Rosenberg, who has experience in purifying and characterizing proteoglycans, Dr. E. J. Miller, who has experience in purification and characterization of collagens, and Dr. L. Reid, a cell biologist who has expertise in culturing differentiated mammalian epithelial cells. This joint venture should maximize the chances of success in developing defined matrix substrata for growth and/or differentiation of epithelial cells. (A)